title: Cytosolic transmitter concentration regulates vesicle cycling at hippocampal GABAergic terminals.
abstract: Sustained synaptic transmission requires vesicle recycling and refilling with transmitter, two processes considered to proceed independently. Contrary to this assumption, we show here that depletion of cytosolic transmitter at GABAergic synapses reversibly reduces the number of recycling vesicles. Using paired recordings in hippocampal cultures, we show that repetitive activity causes two phases of reduction of the postsynaptic response. The first involves the classical depletion of the readily releasable and recycling pools, while the second reflects impairment of vesicle filling as GABA is consumed, since it can only be reversed by uptake of GABA or its precursors, glutamate or glutamine. Surprisingly, this second phase is associated with reduced quantal release, a faster depression rate and lower FM5-95 labeling, suggesting that the size of the cycling vesicular pool is regulated by cytosolic transmitter availability. Regulation of vesicular cycling may represent a general mechanism of presynaptic plasticity, matching synaptic release to transmitter supply.
authors.affiliation: INSERM, U1024, F-75005 Paris, France; CNRS, UMR 8197, F-75005 Paris, France; Ecole Normale Supérieure, Institut de Biologie de l'ENS, IBENS, F-75005 Paris, France; Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, 200062 Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Tu
authors.forename: Laurine
authors.initials: L
authors.lastname: Bonet
authors.forename: Karin R
authors.initials: KR
authors.lastname: Aubrey
authors.forename: Stéphane
authors.initials: S
authors.lastname: Supplisson
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid